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CLINICAL RESEARCH: HEART FAILURE

Clinical Outcomes According to Baseline Blood Pressure in Patients With a Low Ejection Fraction in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Program

Peter A. Meredith, PhD^_*, Jan Östergren, MD, Inder Anand, MD, Margareta Puu, PhD, Scott D. Solomon, MD^||, Eric L. Michelson, MD^¶, Bertil Olofsson, PhD, Christopher B. Granger, MD^#, Salim Yusuf, MB, BS, DPhil^_**, Karl Swedberg, MD, PhD, Marc A. Pfeffer, MD, PhD^|| and John J.V. McMurray, MD^_*,_*

^_* Faculty of Medicine, University of Glasgow, Glasgow, Scotland
Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden
University of Minnesota Medical School and VA Medical Center, Minneapolis, Minnesota
AstraZeneca Research and Development, Mölndal, Sweden
^|| Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
^¶ AstraZeneca LP, Wilmington, Delaware
^# Duke University Medical Center, Durham, North Carolina
^_** HGM-McMaster Clinic, Hamilton, Ontario, Canada
Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Manuscript received June 26, 2008; revised manuscript received August 18, 2008, accepted September 8, 2008.

^_* Reprint requests and correspondence: Dr. John J. V. McMurray, Department of Cardiology, Western Infirmary, Glasgow, G11 6NT, United Kingdom (Email: j.mcmurray{at}bio.gla.ac.uk).

Objectives: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (0.40) in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) program.

Background: Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure. This paradox creates a dilemma for physicians and may explain why low BP is reported as a reason for under-use of these agents.

Methods: The interaction between treatment and baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) was examined with patients divided into 6 SBP categories (100, 101 to 110, 111 to 120, 121 to 130, 131 to 140 and 141 mm Hg) and 4 DBP categories (60, 61 to 70, 71 to 80 and 81 mm Hg).

Results: Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP.

Conclusions: In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.

Key Words: heart failure • angiotensin receptor blockers • blood pressure

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   BP = blood pressure   CV = cardiovascular   DBP = diastolic blood pressure   EF = ejection fraction (left ventricular)   HF = heart failure   NYHA = New York Heart Association   SBP = systolic blood pressure

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